Organic Chemistry Portal
Reactions >> Protecting Groups >> Stability

Benzyl carbamates

Cbz-NR2 / Z-NR2

T. W. Green, P. G. M. Wuts,
Protective Groups in Organic Synthesis,
Wiley-Interscience, New York, 1999, 531-537, 736-739.

 

Stability

H2O: pH < 1, 100C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100C
Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2
Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3
Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH
Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4
Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2/CH2Cl2

Protection of Amino Groups


A simple and efficient protection procedure is general and regioselective for the preparation of mono-N-Boc, N-Cbz, N-Fmoc or N-Alloc aromatic amines in high yield without affecting aliphatic amino groups and other functionalities.
V. Perron, S. Abbott, N. Moreau, D. Lee, C. Penney, B. Zacharie, Synthesis, 2009, 283-289.

Deprotection


In situ preparation of an active Pd/C catalyst from Pd(OAc)2 and charcoal in methanol enables a simple, highly reproducible protocol for the hydrogenation of alkenes and alkynes and for the hydrogenolysis of O-benzyl ethers. Mild reaction conditions and low catalyst loadings, as well as the absence of contamination of the product by palladium residues, make this a sustainable, useful process.
F.-X. Felpin, E. Fouquet, Chem. Eur. J., 2010, 12440-12445.


Ammonia, pyridine and ammonium acetate were extremely effective as inhibitors of Pd/C catalyzed benzyl ether hydrogenolysis. While olefin, Cbz, benzyl ester and azide functionalities were hydrogenated smoothly, benzyl ethers were not cleaved.
H. Sajiki, Tetrahedron Lett., 1995, 36, 3465-3468.


A generally applicable method for the introduction of gaseous hydrogen into a sealed reaction system under microwave irradiation allows the hydrogenation of various substrates in short reaction times with moderate temperatures between 80 C and 100 C with 50 psi of hydrogen.
G. S. Vanier, Synlett, 2007, 131-135.


In situ generation of molecular hydrogen by addition of triethylsilane to palladium on charcoal results in rapid and efficient reduction of multiple bonds, azides, imines, and nitro groups, as well as deprotection of benzyl and allyl groups under mild, neutral conditions.
P. K. Mandal, J. S. McMurray, J. Org. Chem., 2007, 72, 6599-6601.


Various thioureas derived from primary amines and carbamoyl-protected isothiocyanates react with the Burgess reagent to give the corresponding guanidines via either a stepwise or one-pot procedure. A selective deprotection of the N,N′-diprotected guanidines affords N-monoprotected guanidines.
T. Maki, T. Tsuritani, T. Yasukata, Org. Lett., 2014, 16, 1868-1871.

Other Syntheses of Cbz-Protected Amino Groups


An efficient catalytic four-component reaction of carbonyl compounds, benzyl chloroformate, 1,1,1,3,3,3-hexamethyldisilazane, and allyltrimethylsilane provides Cbz-protected homoallylic amines in the presence of 5 mol% of iron(II) sulfate heptahydrate as an inexpensive and environmentally friendly catalyst.
Q.-Y. Song, B.-L. Yang, S.-K. Tian, J. Org. Chem., 2007, 72, 5407-5410.


The reaction of di-tert-butyl dicarbonate or a chloroformate and sodium azide with an aromatic carboxylic acid produces the corresponding acyl azide. The acyl azide undergoes a Curtius rearrangement to form an isocyanate derivative which is trapped either by an alkoxide or by an amine to form the aromatic carbamate or urea.
H. Lebel, O. Leogane, Org. Lett., 2006, 8, 5717-5720.


Cbz-Protected Amino-Groups in Multi-step Syntheses


N-Cbz-protected amino acids reacted with various aryl amines in the presence of methanesulfonyl chloride and N-methylimidazole in dichloromethane to give the corresponding arylamides in high yields without racemization under these mild conditions.
L. Mao, Z. Wang, Y. Li, X. Han, W. Zhou, Synlett, 2011, 129-133.